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https://www.readbyqxmd.com/read/28276094/pathology-of-toxic-leucoencephalopathy-in-drug-abuse-supports-hypoxic-ischemic-pathophysiology-etiology
#1
Murad Alturkustani, Lee-Cyn Ang, David Ramsay
The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes...
March 9, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28270242/to-see-or-not-to-see-non-invasive-imaging-for-improved-readout-of-drug-treatment-trials-in-the-murine-model-of-secondary-alveolar-echinococcosis
#2
D Gorgas, N Marreros, R Rufener, A Hemphill, B Lundström-Stadelmann
Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase...
March 8, 2017: Parasitology
https://www.readbyqxmd.com/read/28260886/convection-enhanced-delivery-of-panobinostat-lbh589-loaded-pluronic-nano-micelles-prolongs-survival-in-the-f98-rat-glioma-model
#3
W G Singleton, A M Collins, A S Bienemann, C L Killick-Cole, H R Haynes, D J Asby, C P Butts, M J Wyatt, N U Barua, S S Gill
BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28241065/repeated-dexamphetamine-treatment-alters-the-dopaminergic-system-and-increases-the-phmri-response-to-methylphenidate
#4
Anouk Schrantee, Jordi L Tremoleda, Marzena Wylezinska-Arridge, Valentine Bouet, Peter Hesseling, Gideon F Meerhoff, Kora M de Bruin, Jan Koeleman, Thomas Freret, Michel Boulouard, Emilie Desfosses, Laurent Galineau, Alessandro Gozzi, François Dauphin, Willy Gsell, Jan Booij, Paul J Lucassen, Liesbeth Reneman
Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28192174/does-genetic-bdnf-deficiency-in-rats-interact-with-neurotransmitter-control-of-prepulse-inhibition-implications-for-schizophrenia
#5
Maarten van den Buuse, Davina Biel, Kathrin Radscheit
Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28138041/translational-pharmacology-of-the-mglur2-preferring-agonist-ly2812223-in-animal-and-human-brain
#6
Christian C Felder, Douglas A Schober, Yuan Tu, Anne T Quets, Hongling Xiao, Marla Watt, Edward R Siuda, Eric S Nisenbaum, Chuanix Xiang, Beverly Heinz, Lourdes Prieto, David L Mc Kinzie, James A Monn
LY2812223 was identified via structure-activity studies arising from the potent mGlu2/3 receptor agonist LY354740 as a selective mGlu2 agonist. This pharmacology was determined using cells stably transfected cells either containing the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human post mortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28135061/neurocytometry-flow-cytometric-sorting-of-specific-neuronal-populations-from-human-and-rodent-brain
#7
David Martin, Jiaxi Xu, Connie Porretta, Charles D Nichols
Flow cytometry has the potential to facilitate understanding of the heterogeneous responses of diverse brain cell populations to a variety of stimuli. However, existing methods of applying flow cytometry to brain tissues are each limited in certain ways. They either require genetically labeled cells to achieve separation of specific populations, are not applicable to previously fixed tissue, or are not compatible with downstream mRNA analysis. Here, we describe a group of related methods that overcome many previous limitations and allow robust sorting and downstream molecular analysis of highly enriched populations of specific neuronal and non-neuronal cells from any mammalian brain...
February 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28110168/ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-uhplc-ms-ms-for-determination-of-ghb-precursors-and-metabolites-in-different-specimens-application-to-clinical-and-forensic-cases
#8
Francesco Paolo Busardò, Chrystalla Kyriakou, Emilia Marchei, Roberta Pacifici, Daniel Sejer Pedersen, Simona Pichini
Gamma-hydroxybutyric acid (GHB) acts as a precursor and metabolite of the inhibitory central nervous system (CNS) neurotransmitter gamma-aminobutyric acid (GABA). Sodium salt of GHB has been used as a medication for narcolepsy and alcohol withdrawal. Moreover, GHB and its precursor gamma-butyrolactone (GBL), are illegal recreational drugs of abuse. A procedure based on ultra-high-performance liquid chromatography tandem mass spectrometry has been developed and validated in plasma, urine, cerebrospinal fluid and hair for acute and chronic exposure to GHB and in seized preparations coming from black market...
January 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28107458/neuropilin-1-involvement-in-choroidal-and-retinal-neovascularisation
#9
Patricia Fernández-Robredo, Senthil Selvam, Michael B Powner, Dawn A Sim, Marcus Fruttiger
PURPOSE: Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1...
2017: PloS One
https://www.readbyqxmd.com/read/28041969/needle-free-injection-of-vesicular-phospholipid-gels-a-novel-approach-to-overcome-an-administration-hurdle-for-semisolid-depot-systems
#10
Michaela Breitsamer, Gerhard Winter
Vesicular phospholipid gels (VPGs) are depot formulations for the sustained release of drugs which are characterized by a high amount of phospholipids in the formulation. They consist of physiological excipients only and therefore display high biocompatibility. Their manufacture is simple, cheap, solvent free, and ideal for the processing of proteins and peptides because of the low stress on the molecule, for example, by elevated temperatures. One major hurdle of VPGs is their high viscosity which makes them hard to almost impossible to inject with conventional, thin needles used for subcutaneous administration...
December 29, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28039081/neurologic-complications-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
REVIEW
Enrico Maffini, Moreno Festuccia, Lucia Brunello, Mario Boccadoro, Luisa Giaccone, Benedetto Bruno
Neurologic complications after hematopoietic stem cell transplantation are frequently life-threatening, and their clinical management can be highly challenging. A wide spectrum of causative factors-including drug-related toxicities; infections sustained by virus, bacteria, or invasive molds; metabolic encephalopathy; cerebrovascular disorders; immune-mediated disorders; and disease recurrence-may lead to potentially lethal complications. Moreover, given that some neurologic complications are not uncommonly diagnosed post mortem, their overall incidence is likely to be underestimated...
December 27, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27993133/synthesis-and-functionalization-of-protease-activated-nanoparticles-with-tissue-plasminogen-activator-peptides-as-targeting-moiety-and-diagnostic-tool-for-pancreatic-cancer
#12
Sophie Dobiasch, Szilard Szanyi, Aleko Kjaev, Jens Werner, Albert Strauss, Christian Weis, Lars Grenacher, Katya Kapilov-Buchman, Liron-Limor Israel, Jean-Paul Lellouche, Erica Locatelli, Mauro Comes Franchini, Jennifer Vandooren, Ghislain Opdenakker, Klaus Felix
BACKGROUND: Functionalized nanoparticles (NPs) are one promising tool for detecting specific molecular targets and combine molecular biology and nanotechnology aiming at modern imaging. We aimed at ligand-directed delivery with a suitable target-biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising targets are galectins (Gal), due to their strong expression in and on PDAC-cells and occurrence at early stages in cancer precursor lesions, but not in adjacent normal tissues...
December 19, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27955679/post-mortem-histopathology-underlying-%C3%AE-amyloid-pet-imaging-following-flutemetamol-f-18-injection
#13
Milos D Ikonomovic, Chris J Buckley, Kerstin Heurling, Paul Sherwin, Paul A Jones, Michelle Zanette, Chester A Mathis, William E Klunk, Aruna Chakrabarty, James Ironside, Azzam Ismail, Colin Smith, Dietmar R Thal, Thomas G Beach, Gill Farrar, Adrian P L Smith
In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [(18)F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups...
December 12, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27932047/disturbances-of-glucose-metabolism-associated-with-the-use-of-psychotropic-drugs-a-post-mortem-evaluation
#14
Cristian Palmiere, Marc Augsburger, Vincent Varlet
Treatment with atypical antipsychotic agents and tetracyclic antidepressants has been associated with impaired glycemic control. Reported complications have included new-onset diabetes mellitus, life-threatening diabetic ketoacidosis and, rarely, death. The study presented herein focuses on biochemical investigations of glucose metabolism in a series of medico-legal cases that revealed the presence of atypical antipsychotic agents (clozapine, olanzapine, quetiapine and risperidone) or mirtazapine at toxicology...
December 5, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27919010/the-role-of-alcohol-dependency-in-deaths-among-people-with-epilepsy-recorded-by-the-national-drug-related-deaths-index-ndrdi-in-ireland-2004-2013
#15
Ena Lynn, Suzi Lyons, Yvonne Langan, Sarah Craig, Colin Doherty
PURPOSE: The aim of this study was to investigate deaths among individuals with epilepsy recorded on the National Drug-Related Deaths Index (NDRDI). METHOD: A descriptive analysis of individuals with a known history of epilepsy in the NDRDI from 2004 to 2013 was undertaken. RESULTS: Between 2004 and 2013, 225 (2%) of the recorded cases had a documented history of epilepsy, 82 (36%) of whom had epilepsy recorded as the cause of death. Of these 82 deaths, the majority were male (60-73%) and half (median age) were aged 47 years or younger...
February 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27913818/-amyloid-positron-emission-tomography-with-18-%C3%A2-f-florbetaben-in-the-diagnostic-workup-of-dementia-patients
#16
S Schönecker, C Prix, T Raiser, N Ackl, E Wlasich, G Stenglein-Krapf, E Mille, M Brendel, O Sabri, M Patt, H Barthel, P Bartenstein, J Levin, A Rominger, A Danek
BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent (18)F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology...
February 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/27898722/suicide-among-young-people-and-adults-in-ireland-method-characteristics-toxicological-analysis-and-substance-abuse-histories-compared
#17
Ella Arensman, Marco Bennardi, Celine Larkin, Amanda Wall, Carmel McAuliffe, Jacklyn McCarthy, Eileen Williamson, Ivan J Perry
OBJECTIVE: Information on factors associated with suicide among young individuals in Ireland is limited. The aim of this study was to identify socio-demographic characteristics and circumstances of death associated with age among individuals who died by suicide. METHODS: The study examined 121 consecutive suicides (2007-2012) occurring in the southern eastern part of Ireland (Cork city and county). Data were obtained from coroners, family informants, and health care professionals...
2016: PloS One
https://www.readbyqxmd.com/read/27872687/determining-the-molecular-pathways-underlying-the-protective-effect-of-non-steroidal-anti-inflammatory-drugs-for-alzheimer-s-disease-a-bioinformatics-approach
#18
Alejo J Nevado-Holgado, Simon Lovestone
Alzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive. In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database) simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin)...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27793687/synthesis-characterization-and-in-vivo-evaluation-of-a-magnetic-cisplatin-delivery-nanosystem-based-on-pmaa-graft-peg-copolymers
#19
Efstathia Voulgari, Aristides Bakandritsos, Sotiris Galtsidis, Vassilis Zoumpourlis, Benjamin P Burke, Gonçalo S Clemente, Christopher Cawthorne, Stephen J Archibald, Jiři Tuček, Radek Zbořil, Vasiliki Kantarelou, Andreas Germanos Karydas, Konstantinos Avgoustakis
The development of anticancer drug delivery systems which retain or enhance the cytotoxic properties of the drug to tumorous tissues, while reducing toxicity to other organs is of key importance. We investigated different poly(methacrylic acid)-g-poly(ethyleneglycol methacrylate) polymers as in situ coating agents for magnetite nanocrystallites. The obtained magnetic nano-assemblies were in turn thoroughly characterized for their structural, colloidal and physicochemical properties (drug loading capacity/release, magnetic field triggered drug release, cell uptake and localization) in order to select the best performing system...
December 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27756689/neuroadaptations-to-antipsychotic-drugs-insights-from-pre-clinical-and-human-post-mortem-studies
#20
Davide Amato, Clare L Beasley, Margaret K Hahn, Anthony C Vernon
Antipsychotic drugs, all of which block the dopamine D2 receptor to a greater or lesser extent, are the mainstay for the pharmacological treatment of schizophrenia. Engaging in a deeper understanding of how antipsychotics act on the brain and body, at the cellular, molecular and physiological level is vital to comprehend both the beneficial and potentially harmful actions of these medications and stimulate development of novel therapeutics. To address this, we review recent advances in our understanding of neuroadaptations to antipsychotics, focusing on (1) treatment efficacy, (2) impact on brain volume and (3) evidence from human post-mortem studies that attempt to dissect neuropathological effects of antipsychotic drugs from organic schizophrenia neurobiology and (4) cardio-metabolic side effects...
October 15, 2016: Neuroscience and Biobehavioral Reviews
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